allele is associated in the GWAS with an odds ratio of 1.5, and allele of a nearby SNP is associated in the replication set with an odds ratio of 1.46, it must be demonstrated that allele and allele carry effects in the same direction. The most straightforward way to assess this is to examine a reference panel, such as the HapMap data, for a relevant population. If this panel shows that allele from SNP 1 and allele from SNP 2 form a two-marker haplotype in 90% of the sample, then this is a reasonable assumption. If however the panel shows that allele from SNP 1 and allele from SNP 2 form the predominant two-marker haplotype, the effect has probably flipped in the replication set. Mapping the effect through the haplotype would be equivalent to observing an odds ratio of 1.5 in the GWAS and 0.685 in the replication set.
